The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort

There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited. The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development. Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out. Thirty-six statistically significant associations considering multiple testing (p